Intermittent fasting (IF) regimens have gained widespread attention in recent years for their possible role in human health and disease risk. In mice, IF schedules that are aligned with sleep-wake cycles appear to positively influence metabolic processes related to cancer risk and may have direct effects on carcinogenesis; however the impact of these regimens on cancer risk in humans remain unclear. We examined associations between nighttime fasting duration (a form of IF aligned with sleep-wake cycles) and (1) biomarkers demonstrated to be associated with breast cancer prognosis; and (2) long-term clinical outcomes in a sample of breast cancer survivors from the Women's Healthy Eating and Living (WHEL) Study.
Dietary data were available for 3,061 non-diabetic women enrolled in the WHEL Study. Nighttime fasting duration was calculated using time-stamped 24-hour dietary recalls collected at the baseline, Year 1, and Year 4 study assessment periods. Approximately 3-4 dietary records were collected per subject at each assessment period, and these records were averaged to yield a single estimate of nighttime fasting duration per time point. Glycosylated hemoglobin (HbA1c) and C-reactive protein (CRP) levels were ascertained from blood specimen collected at baseline. Clinical outcomes recorded during the study follow-up include breast cancer events (recurrence or new primary) and mortality. Linear regression models examined the associations of nighttime fasting with baseline concentrations of HbA1c and CRP. Delayed-entry Cox proportional hazard models were used to assess the association between nighttime fasting duration, recorded at the baseline, Year 1, and Year 4 assessments, with clinical outcomes. These models used a counting process method to account for repeated measures. All models controlled for basic demographic factors, participant characteristics (BMI, comorbidity status, sleep duration), breast cancer characteristics (stage, grade, anti-estrogen use), and dietary variables (total calories, evening calories, eating frequency).
Women fasted an average of 12.5 hours per night (SD=1.6 hours). There were 520 new breast cancer events, and 569 deaths during study follow up. HbA1c level was significantly and inversely related to nighttime fasting duration. Each 2-hour increase in the nighttime fasting duration was associated with a 0.2-unit decrease in HbA1c (β=-0.21; p=0.03 with HbA1c expressed as mmol/mol), and there was no evidence of mediation or effect modification by participant characteristics, e.g., BMI. No associations were observed between nighttime fasting duration and CRP. In longitudinal models, women who fasted less than 13.1 hours per night (bottom two tertiles of nightly fasting distribution) had roughly a 50% higher hazard for experiencing a breast cancer event, compared to women who fasted at least 13.1 hours per night (HR: 1.46; 95%CI: 1.11-1.93; p<0.01). Nighttime fasting duration was not associated with mortality.
Findings suggest that increasing the length of the nighttime fasting interval could be a simple, feasible, and novel strategy to improve glucose control and reduce breast cancer risk. Randomized trials confirming the link between nighttime fasting duration and breast cancer risk are warranted.
Citation Format: Marinac CR, Neslon SH, Natarajan L, Sears DD, Breen CI, Pierce JP, Patterson RE. Intermittent fasting in breast cancer risk and survivorship: Insight from the women's healthy eating and living study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-09-01.